Combination Gene Therapy Using IL-2 and GM-CSF Genes Transferred by a Defective Infectious Single Cycle Herpes Virus (DISC Virus) in Head and Neck Squamous Cell Cancer Model / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is an attenuated virus originally produced as a viral vaccine, but it also serves as an efficient gene transfer vehicle. The main goals of this study were to examine determinants of gene transfer using DISC vectors for squamous cell carcinoma and to evaluate the efficacy of vaccination with the DISC virus carrying a combination of immunomodulatory genes (IL-2, GM-CSF) as cancer therapy in a model of squamous cell cancer in the C3H/HeJ mice. MATERIALS AND METHODS: We determinated the gene and protein expression of DISC-IL-2 and DISC-GM-CSF transfected SCCVII cells by RT-PCR and ELISA method. Also, we evaluated the ex vivo vaccination effects of DISC-IL-2 and DISC-GMCSF on preventing the development of SCCVII tumor. RESULTS: SCCVII cells transduced by the DISC virus vector (MOI=10) carrying the IL-2, or the GM-CSF gene, produced nanogram quantities of IL-2 or GM-CSF per 10(6) cells. Of particular interest was the observation that cells irradiated at different doses (5,000 cGy, 10,000 cGy) secreted levels of GM-CSF or IL-2 that were comparable to non-irradiated cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-IL-2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (p<0.01). Among the multiple immunomodulatory transgenes vaccination groups, the DISC-GMCSF transfected vaccine showed the greatest suppression of tumor development and growth (p<0.001). CONCLUSION: These data demonstrate that: 1) The DISC virus vector is capable of efficient gene transfer to SCCVII cells, 2) The GM-CSF secreting, genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor cell challenge and suppressed tumor growth in our tumor model. The DISC virus-mediated, cytokine gene transfer may prove to be useful in clinical therapy for head and neck cancers.

Invasions and Metastases of Facial and Neck Skin by Head and Neck Cancer / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study was designed to review the incidence of skin involvement in the head and neck cancer. We also reviewed its pattern, treatment results, and prognostic significance of skin invasion and metastases. MATERIALS AND METHODS: We carried out an retrospective evaluation of 41 patients who required resection of the facial or neck skin during surgery for their head and neck cancer in the last ten years. Patients with head and neck skin cancer were excluded from this study. Patients who developed skin involvement were evaluated with regard to the primary origin of tumor, the tumor stage, and the pattern of skin involvement, treatment and outcome. The cases were classified into four groups: firstly, a group with the presence of skin scar made by previous biopsy; secondly, a group with tumor fixed to skin; thirdly, a group with skin resected with a sufficient resection marginal, and lastly a group with gross involvement of skin by tumor. RESULTS: Among 41 patients who required resection of the skin, patients with skin invasion were noted in 24 cases. Only one out of four cases of the biopsy group had skin involvement whereas a half of the fixed group had skin invasion. For the marginal group, only two cases had invasion of skin. The treatment result of patients with skin involvement had poor prognosis compared to patients without skin involvement. In particular, patients with skin metastasis had extremely poor survival. CONCLUSIONS: Skin involvement in the head and neck cancer indicates a poor prognosis, and should not be considered for surgery.

Pathologically Proven Level IIb Lymph Node Metastasis in Head and Neck Cancer: A Preliminary Report / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The spinal accessory nerve dysfunction is a serious sequela following selective neck dissections despite preservation of the spinal accessory nerve. The incidence of this complication is known to be 20%-30% and the primary cause of nerve dysfunction is known as significant traction during resection of level IIb lymph node group. To try to answer whether level IIb could be preserved, we evaluated the incidence of metastasis to level IIb lymph node from various types of the head and neck cancer. MATERIALS AND METHODS: Sixty patients who underwent surgery for their head and neck cancer as an initial treatment from February 1999 to July 2000 were prospectively evaluated. Histopathological evaluations for 106 neck dissection specimens were performed in 60 patients with the head and neck cancer. RESULTS: A total of 7 patients (11.7%) had metastasis to level IIb lymph node. All but one case had ipsilateral level IIb metastasis. All seven cases had multiple lymph node metastases to other levels, including level I, IIa, III, IV, or V. Occult metastasis to level IIb was noted in one case of 25 clinically proven N0 head and neck cancer patients (4%). Primary sites and pathologies with level IIb metastasis were varied, including such sites as upper eyelid, parotid gland, or thyroid gland. CONCLUSIONS: This preliminary report reveals low incidence of level IIb metastasis in some of clinically proven N0 head and neck cancer. Contralateral level IIb lymph node could be preserved in clinically proven N0 heasd and neck cases. Multiple lymph node metastases increase the probability of metastasis to level IIb. Level IIb resection is necessary in clinically proven N+ cases with multiple nodes or multiple levels of metastases. Also, Level IIb metastasis may tend to increase in some of the primary sites, which drain into the jugular chain via level IIb lymph node.

Surgical Treatment of Primary and Metastatic Malignant Tumors of the Accessory Parotid Gland / 대한이비인후과학회지

Abstract Tumor of the accessory parotid gland is frequently mistaken as a cheek subcutaneous tumor because of its location and rarity. Preoperative tissue diagnosis is imperative for proper treatment of this rare tumor. In technical point of view, the parotidectomy approach with wide facial nerve dissection and careful elevation of cheek flap is the key to safe resection of the tumor without complication of facial nerve injury. We report one case each of primary and metastatic cancer of accessory parotid gland with a brief review of literature.

Preliminary Results of Vocal Fold Augmentation by Injection of Autologous Fascia / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Vocal fold augmentation by injection under direct visual control is a quick, easy, and accurate operation. However, when autologous fat or bovine collagen is used, both showed considerable resorption over time and gave variable results. Autologous fascia is a newly introduced graft material and has a low metablolic requirements with also a relatively stable histological characteristics. The goal of this study was to confirm the autologous fascia as a new injection material of vocal fold augmentation and assess the impact of the fascia injection on voice acoustics. MATERIALS AND METHOD: Six subjects with vocal cord palalysis and three with sulcus vocalis were analyzed after injection. The temporalis muscle fascia and abdominal fat were harvested. The fascia was cut into small pieces and injected using the pressure syringe with a 18 G needle on the lateral aspect of the vocal fold under the direct visual control. The preoperative and postoperative parameters including jitter, shimmer, signal to noise ratio, and maximum phonation time were analyzed. RESULTS: There was significant improvement in all parameters measured in the group of vocal cord palsy. But there was no definite improvement in the sulcus vocalis group. There was only one laryngeal complication, the postoperative granuloma at leakage site of injection. CONCLUSION: According to these preliminary results, it is suggested that vocal fold augmentation by injection of autologous fascia can be a stable and effective surgical treatment for vocal cord palsy.